The Metabolic Clinical Research Unit (MRCU) and the Phenotyping Laboratory opened in January 2007 and are the primary sites where this research is conducted. The MCRU is comprised of ten private inpatient rooms modified to accommodate the needs and safety of patients with extreme obesity (class III). See http://www2.niddk.nih.gov/Research/ClinicalResearch/MCRU/. As part of this natural history study, baseline phenotypic data is obtained in subjects of normal weight, overweight and class I, II and III obesity. Participants are provided a summary of clinically useful results that they can share with their physicians in planning weight loss strategies and are invited to return for yearly evaluations. Validation studies to assess the dynamic range and reproducibility of the equipment including the cart and room calorimeters, DEXA and ADP and exercise equipment have been performed. A bank of skeletal muscle, fat and peripheral blood for genomic DNA is being created on the extensively phenotyped subjects and is shared with investigators across the NIH campus. Subject accrual to target inclusion of patients with genotypes associated with weight dysregulation or metabolic disturbance has begun. Subjects participating in weight loss interventions such as bariatric surgery are targeted for follow-up studies to assess changes in body composition and energy expenditure. A collaboration with the NCI Nutritional Epidemiology Branch aims to validate new tools for studying self report of exercise and food intake.